Smith-Lemli-Opitz Syndrome Follow-up

Updated: Sep 24, 2021
  • Author: Robert D Steiner, MD, FAAP, FACMG; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Further Outpatient Care

Early intervention is often useful. In addition, children affected by Smith-Lemli-Opitz syndrome may benefit from receiving follow-up care from a geneticist, metabolic-disease specialist, and/or behavioral/developmental pediatrician familiar with the complications and long-term needs of patients with Smith-Lemli-Opitz syndrome.


Further Inpatient Care

The condition of patients with the most severe type of Smith-Lemli-Opitz syndrome (SLOS), sometimes referred to as Smith-Lemli-Opitz syndrome type II, is characterized by very low plasma cholesterol levels (usually, approximately < 20 mg/dL [as measured by gas chromatography methods to separate sterols]), obtundation or coma, respiratory failure necessitating mechanical ventilation, and multiple malformations manifesting at birth. This condition is almost invariably lethal. The clinician should strongly consider offering palliative care only.


Inpatient & Outpatient Medications

Supplemental cholesterol may be helpful. Clinical trials are ongoing. Fresh frozen plasma and bile acids have sometimes been administered to patients with Smith-Lemli-Opitz syndrome who have very low plasma cholesterol levels or when mildly to moderately affected patients are unable to take their oral cholesterol supplement, often as a result of illness or surgery.



In the newly diagnosed fetus, newborn, or young infant, transfer to a tertiary care academic facility where a medical geneticist or metabolic-disease specialist is immediately available and pediatric general surgeons and appropriate pediatric surgical subspecialists are available may be required. In some cases, the infant may be too ill and unstable to transport.

Transfer or intermittent visits to a facility where active clinical research in Smith-Lemli-Opitz syndrome is ongoing may be considered in any age group.



Photosensitivity may occur; instruct patient to avoid prolonged exposure to sunlight and to judiciously use sunscreens and clothing. Supplemental cholesterol, or even fresh frozen plasma (as a source of cholesterol), may be useful in the short term for patients with Smith-Lemli-Opitz syndrome who require surgery or who are very ill for any reason. Adrenal insufficiency may occur, and glucocorticoid and/or mineralocorticoid supplementation may be needed. [36]



Many possible complications are recognized. Virtually every cell in the body is dependent on cholesterol to maintain normal function; therefore, the cholesterol deficiency in patients with Smith-Lemli-Opitz syndrome can affect every organ.

Those most severely affected with Smith-Lemli-Opitz syndrome are either spontaneously aborted or die in the neonatal period despite maximal therapy.

Many individuals have multiple malformations. Congenital heart disease and brain malformations may be lethal.

Affected individuals who survive may have renal disease, adrenal insufficiency, seizures, failure to thrive, and hepatic dysfunction.



Survival is less likely when the plasma cholesterol level is less than approximately 20 mg/dL as measured by gas chromatography.

Some individuals with Smith-Lemli-Opitz syndrome live into adulthood.

Long-term survival may be more common in the era of cholesterol supplementation. Pauli et al reported a 30-year follow-up of 1 of the 3 original patients described by Smith et al and described the following [37] :

  • Phenotypic manifestation persisted, although the patient's general health had been excellent.

  • He has severe intellectual disability (ID) and expresses violent behavioral outbursts.

  • He is medicated for a seizure disorder and behavior control.

  • His diet analysis showed poor cholesterol intake, which was increased dramatically because of possible benefit of dietary cholesterol supplementation.

  • Two months following initiation of this diet, caregivers described him as calmer, happier, and more verbal.

  • Repeat assessment of plasma cholesterol levels did not demonstrate impressive improvement.

  • Although published data concerning long-term prognosis of patients with Smith-Lemli-Opitz syndrome is scarce, this case report is illustrative.